The number of aging individuals with the vision threatening diseases of diabetic retinopathy (DR) and age- related macular degeneration (AMD) is projected to increase in the coming decades as the aging population of the United States grows. Identifying new modifiable factors that prevent or delay vision threatening disease is significant because it will reduce the burden of health care costs for treatment of such chronic diseases and extend the years that the elderly can be independent and participate in such vision dependent activities as driving, reading, exercise, and food preparation. Vitamin D deficiency and inadequacy is prevalent in a large portion of the aging US population, and vitamin D has been shown to have anti-inflammatory and anti- angiogenic properties, in addition to potentially modulating blood pressure and glucose control. The long-term goal of the proposed research is to better understand the role of vitamin D status in retinal diseases highly prevalent in aging individuals. Minimal research has investigated the association between vitamin D status and DR; although a strong biologic rationale supports vitamin D status as a potential modifiable risk factor for DR development and progression. At the same time, research in two large epidemiologic studies show that people with vitamin D deficiency or inadequacy (25-hydroxyvitamin D (25(OH)D)<50 nmol/L) are more likely to have prevalent AMD, but no prospective studies of AMD incidence and vitamin D status have been conducted. We hypothesize that individuals with deficient or inadequate vitamin D status, compared to individuals with adequate status, will be more likely to have AMD and DR and be more likely to develop AMD. The purpose of this proposal is to investigate associations between vitamin D status and both DR and AMD using data from the aging (45-64 years) Atherosclerosis Risk in Communities (ARIC) population-based, biracial (African American and Caucasian) cohort. We propose to use previously collected data, including graded retinal photographs for DR and AMD status, and assayed serum 25(OH)D concentrations from ARIC study participants collected from 1987-1995, as well as graded retinal photographs currently being obtained in a follow-up study (2011-2013). Specifically, we propose to investigate the association between vitamin D status, assessed at Visit 2 (1990-1992), and 1) the presence of DR assessed at Visit 3 (1993-1995) among 1,657 individuals with diabetes and 2) the presence of AMD assessed at Visit 3 (1993-1995) among 11,532 participants. Third, we also proposed to investigate, for the first time, the association between vitamin D status, assessed in 1990-1992, and the incidence or progression of AMD (from 1993-1995 to 2011-2013) in a sample of approximately 2,346 ARIC participants. This study will advance our understanding of vitamin D status in relation to common vision-threatening eye diseases in the elderly and could lead to new therapies for the prevention or reduced progression of these diseases. PUBLIC HEALTH RELEVANCE: Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are common vision-threatening eye diseases among the elderly. Current work suggests that persons with adequate vitamin D status are less likely to have AMD, but little work exists on the relationship of vitamin D and DR. Using data from a population-based, longitudinal study of aging African American and Caucasian men and women, we purpose to investigate the association between vitamin D status and prevalent DR and AMD; and second, we propose to investigate, for the first time, the association between vitamin D status and incidence or progression of AMD.